This project aims to isolate and characterize putative endogenous tumor promoters and to develop a rapid and economical assay for identification of exogenous and endogenous tumor promoters. The following activities were specifically pursued: (1) elucidation of the mechanism of 12-0- tetradecanoyl-phorbol-13-acetata (TPA)-induced inhibition of epidermal growth factor (EGF) binding (TIEB) and search for a compound(s) which can reverse and modulate TIEB at nontoxic doses; (2) isolation and characterization of membrane receptors of phorbol esters; (3) search for endogenous ligand(s) for phorbol receptors, and their isolation and characterizaiton; (4) isolation and characterization of growth factor(s) induced by biologically active phobol esters; (5) test whether EGF and other growth factors enhance carcinogenesis in vivo and in vitro; (6) investigate whether TPA induces or enhances the expression of endogenous oncogenic cellular information; (7) study whether retroviruses act as promoters in carcinogenesis initiated by chemical or physical agents; (8) reversal of anchorage independent growth of transformed cells by differentiation inducing agents; (9) isolation and characterization of TPA binding protein; (10) study of the catabolism of phorbol diesters.